First-in-human phase I trial of two schedules of OSI-930, a novel multikinase inhibitor, incorporating translational proof-of-mechanism studies.

Purpose: OSI-930 is a novel, potent, oral small-molecule receptor tyrosine kinase inhibitor, predominantly against VEGF receptors (VEGFR), c-Kit, and platelet-derived growth factor receptors. A phase I trial was undertaken to determine safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and antitumor activity of OSI-930 in patients with advanced solid tumors.

Experimental Design: OSI-930 was administered once or twice a day using a modified accelerated titration design.

How to assess anti-tumour efficacy by imaging techniques.

Response evaluation in the assessment of potential new anti-cancer therapies is undergoing intense investigation and change. Current imaging techniques most commonly used in early phase clinical trials are limited to providing reliable and reproducible anatomical data demonstrating a change in size and reduction in tumour volume thereby inferring patient benefit. Current imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) by their nature require computer programs and software.

Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial.

Background: In the non-curative setting, the sequence in which anticancer agents are used, singly or in combination, may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects. We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer, who were regarded as not potentially curable irrespective of response.

Methods: We studied patients with advanced colorectal cancer, starting treatment with non-curative intent.